The present work is on the total synthesis of a natural compound found in a mixture of secondary metabolite produced by an alga nearby the cost of Australia. The target molecule, the 4bromo3butyl5(dibromomethylene)furan2(5H)one, has not previously been proposed. The synthetic route described in this thesis uses cheap and readily available starting materials and the target is reached after six synthetic steps. Several new results have been obtained: selective monolithiation of a dibromofuran; Suzuki coupling with butyl boronic acid; a regioselective photooxidation of furan. The final step of the synthesis, a dibromoolefination, has not yet been accomplished.
Master’s Thesis in Organic Chemistry ON THE SYNTHESIS OF A FIMBROLIDE Alexandre Descomps June, 2008 Faculty of Science Department of Chemistry University of Tromsø Master’s Thesis in Chemistry ON THE SYNTHESIS OF A FIMBROLIDE Alexandre Descomps June, 2008 To my ‘girls’, Anastassia and Valentine contents CONTENTS ACKNOWLEDGMENTS LIST OF ABBRVIATIONS AND SYMBOLS SUMMARY CHAPTER INTRODUCTION: some personal reflexions 1 Statement of the project Methodology CHAPTER BACKGROUND INFORMATION Some biology About the objective 3 Previous attempts of synthesis a The First attempt b Trough a β-lithio carboxylate c Bromolactonisation of the 2-butyl-2, 3-pentadienoate d Synthesis of Acetoxyfimbrolide e With the butylmaleic acid as a precursor 10 Some conclusions 11 References 12 CHAPTER Contents THEORITICAL PART 15 Description of the molecule 15 Retrosynthetic strategy 16 Description of the possible reactions available 17 a Formation of the 3,4-dibromofuran 17 b The 3-Alkylation of the furan 18 c Regioselective photooxidation 21 d Protection step 24 e Dibromoolefination 26 f The Mucobromic acid route 32 g Oxidation of the hydroxyl group 35 References 36 CHAPTER RESULTS AND DISCUSSIONS 39 Synthesis of the 3,4-dibromofuran 39 Synthesis of the 3-bromo-4-butylfuran 40 Synthesis of the 3-bromo-4-butyl-5-hydroxyfuran-2(5H)-one 45 Protection of the hydroxyl group 48 a The THP protection 48 b The metoxy protection 48 Dibromoolefination 49 a Attempts with Dibromotriphenylphosphine bromide and t-BuOK 49 b Attempts with dibromotriphenylphosphonium bromide and activated zinc 50 c Attempts with (bromomethyl)triphenylphosphonium bromide and t-BuOk 51 Suzuki compling on protected Mucobromic acid 52 Contents References 54 CHAPTER SOME KIND OF CONCLUSIONS 57 CHAPTER EXPERIMENTAL PART 61 Materials 61 Substance Identification 62 Generals Procedures 63 a Synthesis of the 3,4-dibromofuran 63 b Synthesis of the 3-bromo-4-butylfuran 64 c Synthesis of the 3-bromo-4-butyl-5-hydroxyfuran-2(5H)-one 66 d Synthesis of the dibromotriphenylphosphonium bromide 67 e Synthesis of activated zinc 68 f Synthesis of (bromomethyl)triphenylphosphonium bromide 69 g Synthesis of the O-Tetrahydropanyl Mucobromic acid derivative 70 h Synthesis of the methoxy protected Mucobromic acid 71 f Synthesis of 3-bromo-4-butyl-5-methoxyfuran-2(5H)-one 72 CHAPITRE FURTHER CONSIDERATIONS 75 CHAPTER APPENDICES 79 Acknowledgements Appendices 87 Appendices 88 Appendices 89 Appendices 90 Appendices 91 Appendices 92 Appendices 93 Appendices 94 Appendices 95 Appendices 96 Appendices 97 Appendices 98 Appendices 99 Appendices 100 Appendices 101